MDS patients harboring acquired activating mutations in the FLT3 receptor tyrosine kinase tend to progress to acute myeloid leukemia (AML) significantly more rapidly and with higher frequency than those without FLT3 mutations. Therefore, FLT3 mutations are likely to contribute to the progression from MDS to AML. With current FLT3 mutation detection methods, a detection limit of 5-10% can be achieved. In MDS samples the percentage of blast cells that carry FLT3 mutations is expected to be very low. A new detection method with greater sensitivity than the current approaches would enable FLT3 mutant MDS patient samples to be accurately classified as such as early as possible. Our strategy is to apply next-generation sequencing methods to detect these mutations that may occur with a very low frequency. By detecting the presence of mutations at an earlier stage, we may be able to create a new opportunity for intervention with a next-generation FLT3 kinase inhibitor. PUBLIC HEALTH RELEVANCE: Myelodysplastic syndrome is a chronic condition involving persistent peripheral blood cytopenias secondary to bone marrow dysfunction, and typically has a poor outcome. We aim to develop a more sensitive predictive assay that can be used to identify patients at high risk for progressing to leukemia, and which therefore may help to improve treatment of the disease.